Individual and Combined Associations of Fasting Serum Lipids with Incident Risk of First Ischemic Stroke: A Chinese Community-Based Nested Case-Control Study

Background: Dyslipidemia is a well-recognized risk factor of cardiovascular diseases. But its role in first ischemic stroke (IS) remains perplexing. Our study evaluated individual and combined associations of specific types of fasting blood lipids with first IS. Methods: The study sample population was drawn from a community-based cohort study of hypertension in Lianyuangang and Rongcheng, China, using a nested case-control design, including 2463 identified first IS cases and 2463 controls, matched by age±1 year, sex and region . Conditional logistic regression was used to estimate odds ratios (OR) and 95% confident intervals (CI) of first IS, after adjustment for pertinent covariates. Findings: High-density lipoprotein cholesterol (HDL-C) was inversely associated with first IS (adjusted OR: 0·91; 95% CI: 0·85-0·98; P=0·014). A positive association between triglycerides (TG) and first IS (aOR:1·10; 95% CI: 1·02-1·17; P=0·007) was found. There was a positive but non-significant association between low-density lipoprotein cholesterol (LDL-C) and first IS (aOR:1·04; 95% CI:0·97-1·12; P=0·239). When LDL-C or TG was combined with HDL-C for analysis, a significant risk association with first IS was found among those with low HDL (< 53·0 mg/dL) and high LDL-C (≥138·1 mg/dL) (aOR: 1·66; 95%CI: 1·19-2·31; P=0·003) or those with low HDL (< 53·0 mg/dL) and high TG (≥140·8 mg/dL) (aOR: 1·47; 95%CI: 1·17-1·84; P<0·001). Interpretation: In this Chinese hypertensive population, higher HDL-C was a significant protective factor, while higher TG was a significant risk factor. And elevated LDL-C and TG were no longer associated with first IS in the presence of higher HDL-C. These results, if further confirmed, underscore the importance of optimizing HDL-C levels, likely higher than the current clinical threshold, in the primary prevention of IS. Funding: The study was funded by the following: the National Key Research and Development Program [2016YFE0205400, 2018ZX09739, 2018ZX09301034003], the Science and Technology Planning Project of Guangzhou, China [201707020010]; the Science, Technology and Innovation Committee of Shenzhen [JSGG20170412155639040, GJHS20170314114526143, JSGG20180703155802047]; the Economic, Trade and Information Commission of Shenzhen Municipality [20170505161556110, 20170505160926390], the Jiangxi Outstanding Person Foundation [20192BCBL23024], Major projects of the Science and Technology Department, Jiangxi [20171BAB205008];the Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (Grant No. PWZxq2017-08) and the National Nature Science Foundation of China (Grant No. 81601010, 81960074, 81500233). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: This study was approved by the Ethics Committee of the Institute of Biomedicine, Anhui Medical University, Hefei, China, the Ethics Committee of Lianyungang Precision Health Institute, and the Ethics Committee of the Lianyungang Center for Advanced Research in Cardiovascular Diseases. All participants provided written informed consent.